The 100 most-cited articles in Critical Care Medicine, 2016

OBJECTIVE: To provide clinicians with evidence-based strategies to optimize the support of the family of critically ill patients in the ICU. METHODS: We used the Council of Medical Specialty Societies principles for the development of clinical guidelines as the framework for guideline development. We assembled an international multidisciplinary team of 29 members with expertise in guideline development, evidence analysis, and family-centered care to revise the 2007 Clinical Practice Guidelines for support of the family in the patient-centered ICU. We conducted a scoping review of qualitative research that explored family-centered care in the ICU. Thematic analyses were conducted to support Population, Intervention, Comparison, Outcome question development. Patients and families validated the importance of interventions and outcomes. We then conducted a systematic review using the Grading of Recommendations, Assessment, Development and Evaluations methodology to make recommendations for practice. Recommendations were subjected to electronic voting with pre-established voting…

PRELIMINARY REMARKS (INTENT OF GUIDELINES) A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals. The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of clinical nutrition and metabolism. The mission of SCCM is to secure the highest quality care for all critically ill and injured patients. Guideline Limitations: These A.S.P.E.N.−SCCM Clinical Guidelines are based on general conclusions of health professionals who, in developing such guidelines, have balanced potential benefits to be derived from a particular mode of medical therapy against certain risks inherent with such therapy. However, practice guidelines are not intended as absolute requirements. The use of these practice guidelines does not in any way project or guarantee any specific benefit in outcome or survival. The judgment of the healthcare professional based on individual circumstances of the patient must always take precedence over the recommendations in these guidelines. The guidelines offer basic recommendations that are…

OBJECTIVES: To update the Society of Critical Care Medicine's guidelines for ICU admission, discharge, and triage, providing a framework for clinical practice, the development of institutional policies, and further research. DESIGN: An appointed Task Force followed a standard, systematic, and evidence-based approach in reviewing the literature to develop these guidelines. MEASUREMENTS AND MAIN RESULTS: The assessment of the evidence and recommendations was based on the principles of the Grading of Recommendations Assessment, Development and Evaluation system. The general subject was addressed in sections: admission criteria and benefits of different levels of care, triage, discharge timing and strategies, use of outreach programs to supplement ICU care, quality assurance/improvement and metrics, nonbeneficial treatment in the ICU, and rationing considerations. The literature searches yielded 2,404 articles published from January 1998 to October 2013 for review. Following the appraisal of the literature, discussion, and consensus, recommendations were written. CONCLUSION: Although…

OBJECTIVE: Machine learning methods are flexible prediction algorithms that may be more accurate than conventional regression. We compared the accuracy of different techniques for detecting clinical deterioration on the wards in a large, multicenter database. DESIGN: Observational cohort study. SETTING: Five hospitals, from November 2008 until January 2013. PATIENTS: Hospitalized ward patients INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Demographic variables, laboratory values, and vital signs were utilized in a discrete-time survival analysis framework to predict the combined outcome of cardiac arrest, intensive care unit transfer, or death. Two logistic regression models (one using linear predictor terms and a second utilizing restricted cubic splines) were compared to several different machine learning methods. The models were derived in the first 60% of the data by date and then validated in the next 40%. For model derivation, each event time window was matched to a non-event window. All models were compared to each other and to the Modified Early Warning score, a…

OBJECTIVES: To provide an appraisal of the evolving paradigms in the pathophysiology of sepsis and propose the evolution of a new phenotype of critically ill patients, its potential underlying mechanism, and its implications for the future of sepsis management and research. DESIGN: Literature search using PubMed, MEDLINE, EMBASE, and Google Scholar. MEASUREMENTS AND MAIN RESULTS: Sepsis remains one of the most debilitating and expensive illnesses, and its prevalence is not declining. What is changing is our definition(s), its clinical course, and how we manage the septic patient. Once thought to be predominantly a syndrome of over exuberant inflammation, sepsis is now recognized as a syndrome of aberrant host protective immunity. Earlier recognition and compliance with treatment bundles has fortunately led to a decline in multiple organ failure and in-hospital mortality. Unfortunately, more and more sepsis patients, especially the aged, are suffering chronic critical illness, rarely fully recover, and often experience an indolent death. Patients with chronic critical illness often…

OBJECTIVE: To update the 2002 version of "Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient." DESIGN: A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. METHODS: Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which…

OBJECTIVE: Initial success with chimeric antigen receptor-modified T cell therapy for relapsed/refractory acute lymphoblastic leukemia is leading to expanded use through multicenter trials. Cytokine release syndrome, the most severe toxicity, presents a novel critical illness syndrome with limited data regarding diagnosis, prognosis, and therapy. We sought to characterize the timing, severity, and intensive care management of cytokine release syndrome after chimeric antigen receptor-modified T cell therapy. DESIGN: Retrospective cohort study. SETTING: Academic children's hospital. PATIENTS: Thirty-nine subjects with relapsed/refractory acute lymphoblastic leukemia treated with chimeric antigen receptor-modified T cell therapy on a phase I/IIa clinical trial (ClinicalTrials.gov number NCT01626495). INTERVENTIONS: All subjects received chimeric antigen receptor-modified T cell therapy. Thirteen subjects with cardiovascular dysfunction were treated with the interleukin-6 receptor antibody tocilizumab. MEASUREMENTS AND MAIN RESULTS: Eighteen subjects (46%) developed grade 3-4 cytokine…

Objective: To establish evidence-based guidelines for the use of bedside cardiac ultrasound, echocardiography, in the ICU and equivalent care sites. Methods: Grading of Recommendations, Assessment, Development and Evaluation system was used to rank the “levels” of quality of evidence into high (A), moderate (B), or low (C) and to determine the “strength” of recommendations as either strong (strength class 1) or conditional/weak (strength class 2), thus generating six “grades” of recommendations (1A–1B–1C–2A–2B–2C). Grading of Recommendations, Assessment, Development and Evaluation was used for all questions with clinically relevant outcomes. RAND Appropriateness Method, incorporating the modified Delphi technique, was used in formulating recommendations related to terminology or definitions or in those based purely on expert consensus. The process was conducted by teleconference and electronic-based discussion, following clear rules for establishing consensus and agreement/disagreement. Individual panel members provided full disclosure and were judged to be free of any commercial…

OBJECTIVES: To synthesize data on prevalence, natural history, risk factors, and post-ICU interventions for depressive symptoms in ICU survivors. DATA SOURCES: PubMed, EMBASE, Cumulative Index of Nursing and Allied Health Literature, PsycINFO, and Cochrane Controlled Trials Registry (1970-2015). STUDY SELECTION: Studies measuring depression after hospital discharge using a validated instrument in more than 20 adults from non-specialty ICUs. DATA EXTRACTION: Duplicate independent review and data abstraction. DATA SYNTHESIS: The search identified 27,334 titles, with 42 eligible articles on 38 unique studies (n = 4,113). The Hospital Anxiety and Depression Scale-Depression subscale was used most commonly (58%). The pooled Hospital Anxiety and Depression Scale-Depression subscale prevalence (95% CI) of depressive symptoms at a threshold score greater than or equal to 8 was 29% (22-36%) at 2-3 months (12 studies; n = 1,078), 34% (24-43%) at 6 months (seven studies; n = 760), and 29% (23-34%) at 12-14 months (six studies; n = 1,041). The prevalence of suprathreshold depressive symptoms…

OBJECTIVES: To track compliance by an interprofessional team with the Awakening and Breathing Coordination, Choice of drugs, Delirium monitoring and management, Early mobility, and Family engagement (ABCDEF) bundle in implementing the Pain, Agitation, and Delirium guidelines. The aim was to study the association between ABCDEF bundle compliance and outcomes including hospital survival and delirium-free and coma-free days in community hospitals. DESIGN: A prospective cohort quality improvement initiative involving ICU patients. SETTING: Seven community hospitals within California's Sutter Health System. PATIENTS: Ventilated and nonventilated general medical and surgical ICU patients enrolled between January 1, 2014, and December 31, 2014. MEASUREMENTS AND MAIN RESULTS: Total and partial bundle compliance were measured daily. Random effects regression was used to determine the association between ABCDEF bundle compliance accounting for total compliance (all or none) or for partial compliance ("dose" or number of bundle elements used) and outcomes of hospital survival and delirium-free…

OBJECTIVES: Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis. DESIGN: Observational cohort study. SETTING: Seven hundred and thirty ICUs in 84 countries. PATIENTS: All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission. MEASUREMENTS AND MAIN RESULTS: ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (-90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (-951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher…

OBJECTIVES: Sarcopenia is associated with a poor prognosis in the ICU. The purpose of this study was to describe a simple sarcopenia index using routinely available renal biomarkers and evaluate its association with muscle mass and patient outcomes. DESIGN: A retrospective cohort study. SETTING: A tertiary-care medical center. PATIENTS: High-risk adult ICU patients from October 2008 to December 2010. INTERVENTIONS: The gold standard for muscle mass was quantified with the paraspinal muscle surface area at the L4 vertebrae in the subset of individuals with an abdominal CT scan. Using Pearson's correlation coefficient, serum creatinine-to-serum cystatin C ratio was found to be the best performer in the estimation of muscle mass. The relationship between sarcopenia index and hospital and 90-day mortality, and the length of mechanical ventilation was evaluated. MEASUREMENTS AND MAIN RESULTS: Out of 226 enrolled patients, 123 (54%) were female, and 198 (87%) were white. Median (interquartile range) age, body mass index, and body surface area were 68 (57-77) years, 28 (24-34) kg/m, and…

OBJECTIVES: The Society of Critical Care Medicine and four other major critical care organizations have endorsed a seven-step process to resolve disagreements about potentially inappropriate treatments. The multiorganization statement (entitled: An official ATS/AACN/ACCP/ESICM/SCCM Policy Statement: Responding to Requests for Potentially Inappropriate Treatments in Intensive Care Units) provides examples of potentially inappropriate treatments; however, no clear definition is provided. This statement was developed to provide a clear definition of inappropriate interventions in the ICU environment. DESIGN: A subcommittee of the Society of Critical Care Medicine Ethics Committee performed a systematic review of empirical research published in peer-reviewed journals as well as professional organization position statements to generate recommendations. Recommendations approved by consensus of the full Society of Critical Care Medicine Ethics Committees and the Society of Critical Care Medicine Council were included in the statement. MEASUREMENTS AND MAIN RESULTS: ICU interventions should…

OBJECTIVE: To determine if intravenous thiamine would reduce lactate in patients with septic shock. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Two US hospitals. PATIENTS: Adult patients with septic shock and elevated (> 3 mmol/L) lactate between 2010 and 2014. INTERVENTIONS: Thiamine 200 mg or matching placebo twice daily for 7 days or until hospital discharge. MEASUREMENTS AND MAIN RESULTS: The primary outcome was lactate levels 24 hours after the first study dose. Of 715 patients meeting the inclusion criteria, 88 patients were enrolled and received study drug. There was no difference in the primary outcome of lactate levels at 24 hours after study start between the thiamine and placebo groups (median: 2.5 mmol/L [1.5, 3.4] vs. 2.6 mmol/L [1.6, 5.1], p = 0.40). There was no difference in secondary outcomes including time to shock reversal, severity of illness and mortality. 35% of the patients were thiamine deficient at baseline. In this predefined subgroup, those in the thiamine treatment group had statistically significantly lower lactate levels at 24…

1Critical Care Educator and Consultant, Glenbrook, NV. 2Education, Development, and Research, University of California San Diego Health, San Diego, CA. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: [email protected]

OBJECTIVES: To elucidate the epidemiology, complication profiles, hospital outcome, and predisposing factors of CNS complications occurring during venoarterial extracorporeal membrane oxygenation in adults. DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization registry. SETTING: Data reported to Extracorporeal Life Support Organization by 230 extracorporeal membrane oxygenation centers from 1992 to 2013. PATIENTS: Patients more than 16 years old supported with a single-run of venoarterial extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We examined 4,522 adult patients supported with venoarterial extracorporeal membrane oxygenation and included in the Extracorporeal Life Support Organization registry. Venoarterial extracorporeal membrane oxygenation was used for cardiac dysfunction in 3,005 patients (66.5%), cardiopulmonary resuscitation in 877 patients (19.4%), and respiratory failure in 640 patients (14.1%), respectively. Multivariate logistic regression was performed to identify factors independently associated with…

OBJECTIVES: To describe the quality of life among sepsis survivors. DESIGN: Secondary analyses of two international, randomized clinical trials (A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis [derivation cohort] and PROWESS-SHOCK [validation cohort]). SETTING: ICUs in North and South America, Europe, Africa, Asia, and Australia. PATIENTS: Adults with severe sepsis. We analyzed only patients who were functional and living at home without help before sepsis hospitalization (n = 1,143 and 987 from A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis and PROWESS-SHOCK, respectively). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis and PROWESS-SHOCK, the average age of patients living at home independently was 63 and 61 years; 400 (34.9%) and 298 (30.2%) died by 6 months. In A Controlled Comparison of Eritoran and placebo in patients with Severe Sepsis, 580 patients had a quality of life measured using EQ-5D at 6 months. Of these, 41.6% could not…

OBJECTIVES: To determine if the early goal-directed mobilization intervention could be delivered to patients receiving mechanical ventilation with increased maximal levels of activity compared with standard care. DESIGN: A pilot randomized controlled trial. SETTING: Five ICUs in Australia and New Zealand. PARTICIPANTS: Fifty critically ill adults mechanically ventilated for greater than 24 hours. INTERVENTION: Patients were randomly assigned to either early goal-directed mobilization (intervention) or to standard care (control). Early goal-directed mobilization comprised functional rehabilitation treatment conducted at the highest level of activity possible for that patient assessed by the ICU mobility scale while receiving mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The ICU mobility scale, strength, ventilation duration, ICU and hospital length of stay, and total inpatient (acute and rehabilitation) stay as well as 6-month post-ICU discharge health-related quality of life, activities of daily living, and anxiety and depression were recorded. The mean age was 61 years and…

OBJECTIVE: Passive leg raising creates a reversible increase in venous return allowing for the prediction of fluid responsiveness. However, the amount of venous return may vary in various clinical settings potentially affecting the diagnostic performance of passive leg raising. Therefore we performed a systematic meta-analysis determining the diagnostic performance of passive leg raising in different clinical settings with exploration of patient characteristics, measurement techniques, and outcome variables. DATA SOURCES: PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and citation tracking of relevant articles. STUDY SELECTION: Clinical trials were selected when passive leg raising was performed in combination with a fluid challenge as gold standard to define fluid responders and non-responders. DATA EXTRACTION: Trials were included if data were reported allowing the extraction of sensitivity, specificity, and area under the receiver operating characteristic curve. DATA SYNTHESIS: Twenty-three studies with a total of 1,013 patients and 1,034 fluid challenges were…

Burnout syndrome (BOS) occurs in all types of healthcare professionals and is especially common in individuals who care for critically ill patients. The development of BOS is related to an imbalance of personal characteristics of the employee and work-related issues or other organizational factors. BOS is associated with many deleterious consequences, including increased rates of job turnover, reduced patient satisfaction, and decreased quality of care. BOS also directly affects the mental health and physical well-being of the many critical care physicians, nurses, and other healthcare professionals who practice worldwide. Until recently, BOS and other psychological disorders in critical care healthcare professionals remained relatively unrecognized. To raise awareness of BOS, the Critical Care Societies Collaborative (CCSC) developed this call to action. The present article reviews the diagnostic criteria, prevalence, causative factors, and consequences of BOS. It also discusses potential interventions that may be used to prevent and treat BOS. Finally, we urge multiple…

OBJECTIVES: Stroke volume variation and pulse pressure variation do not reliably predict fluid responsiveness during low tidal volume ventilation. We hypothesized that with transient increase in tidal volume from 6 to 8 mL/kg predicted body weight, that is, "tidal volume challenge," the changes in pulse pressure variation and stroke volume variation will predict fluid responsiveness. DESIGN: Prospective, single-arm study. SETTING: Medical-surgical ICU in a university hospital. PATIENTS: Adult patients with acute circulatory failure, having continuous cardiac output monitoring, and receiving controlled low tidal volume ventilation. INTERVENTIONS: The pulse pressure variation, stroke volume variation, and cardiac index were recorded at tidal volume 6 mL/kg predicted body weight and 1 minute after the "tidal volume challenge." The tidal volume was reduced back to 6 mL/kg predicted body weight, and a fluid bolus was given to identify fluid responders (increase in cardiac index > 15%). The end-expiratory occlusion test was performed at tidal volumes 6 and 8 mL/kg predicted body weight…

OBJECTIVES: To evaluate the study designs and measurement instruments used to assess physical, cognitive, mental health, and quality of life outcomes of survivors of critical illness over more than 40 years old as a first step toward developing a core outcome set of measures for future trials to improve outcomes in ICU survivors. DESIGN: Scoping review. SETTING: Published articles that included greater than or equal to one postdischarge measure of a physical, cognitive, mental health, or quality of life outcome in more than or equal to 20 survivors of critical illness published between 1970 and 2013. Instruments were classified using the World Health Organization's International Classification of Functioning, Disability, and Health framework. SUBJECTS: ICU survivors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We reviewed 15,464 abstracts, and identified 425 eligible articles, including 31 randomized trials (7%), 116 cross-sectional studies (27%), and 278 cohort studies (65%). Cohort studies had a median (interquartile range) sample size of 96 survivors (52-209), with 38%…

OBJECTIVES: To analyze patterns of critical care medicine beds, use, and costs in acute care hospitals in the United States and relate critical care medicine beds and use to population shifts, age groups, and Medicare and Medicaid beneficiaries from 2000 to 2010. DESIGN: Retrospective study of data from the federal Healthcare Cost Report Information System, American Hospital Association, and U.S. Census Bureau. SUBJECTS: None. INTERVENTIONS: None. SETTING: Acute care U.S. hospitals with critical care medicine beds. MEASUREMENTS AND MAIN RESULTS: From 2000 to 2010, U.S. hospitals with critical care medicine beds decreased by 17% (3,586-2,977), whereas the U.S. population increased by 9.6% (282.2-309.3M). Although hospital beds decreased by 2.2% (655,785-641,395), critical care medicine beds increased by 17.8% (88,235-103,900), a 20.4% increase in the critical care medicine-to-hospital bed ratio (13.5-16.2%). There was a greater percentage increase in premature/neonatal (29%; 14,391-18,567) than in adult (15.9%; 71,978-83,417) or pediatric (2.7%; 1,866-1,916) critical care medicine…

OBJECTIVES: Recent literature has drawn attention to the potential inadequacy of frequentist analysis and threshold p values as tools for reporting outcomes in clinical trials. The fragility index, which is a measure of how many events the statistical significance of a result depends on, has been suggested as a means to aid the interpretation of trial results. This study aimed to calculate the fragility index of clinical trials in critical care medicine reporting a statistically significant effect on mortality (increasing or decreasing mortality). DATA SOURCES: Literature search (PubMed/MEDLINE) to identify all multicenter randomized controlled trials in critical care medicine. STUDY SELECTION: We identified 862 trials; of which 56 fulfilled eligibility criteria and were included in our analysis. DATA EXTRACTION: Calculation of fragility index for trials reporting a statistically significant effect on mortality, and analysis of the relationship between trial characteristics and fragility index. DATA SYNTHESIS: The median fragility index was 2 (interquartile range, 1-3.5), and…

OBJECTIVE: Emerging evidence has shown the potential risks of arterial hyperoxia, but the lack of a clinical definition and methodologic limitations hamper the interpretation and clinical relevance of previous studies. Our purpose was to evaluate previously used and newly constructed metrics of arterial hyperoxia and systematically assess their association with clinical outcomes in different subgroups in the ICU. DESIGN: Observational cohort study. SETTING: Three large tertiary care ICUs in the Netherlands. PATIENTS: A total of 14,441 eligible ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 295,079 arterial blood gas analyses, including the PaO2, between July 2011 and July 2014 were extracted from the patient data management system database. Data from all admissions with more than one PaO2 measurement were supplemented with anonymous demographic and admission and discharge data from the Dutch National Intensive Care Evaluation registry. Mild hyperoxia was defined as PaO2 between 120 and 200 mm Hg; severe hyperoxia as PaO2 greater than 200 mm Hg.…

OBJECTIVES: Time to clearance of pathogens is probably critical to outcome in septic shock. Current guidelines recommend intervention for source control within 12 hours after diagnosis. We aimed to determine the epidemiology of source control in the management of sepsis and to analyze the impact of timing to source control on mortality. DESIGN: Prospective observational analysis of the Antibiotic Intervention in Severe Sepsis study, a Spanish national multicenter educational intervention to improve antibiotherapy in sepsis. SETTING: Ninety-nine medical-surgical ICUs in Spain. PATIENTS: We enrolled 3,663 patients with severe sepsis or septic shock during three 4-month periods between 2011 and 2013. INTERVENTIONS: Source control and hospital mortality. MEASUREMENTS AND MAIN RESULTS: A total of 1,173 patients (32%) underwent source control, predominantly for abdominal, urinary, and soft-tissue infections. Compared with patients who did not require source control, patients who underwent source control were older, with a greater prevalence of shock, major organ dysfunction, bacteremia,…

OBJECTIVE: To provide a management approach for adults with calcium channel blocker poisoning. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Following the Appraisal of Guidelines for Research & Evaluation II instrument, initial voting statements were constructed based on summaries outlining the evidence, risks, and benefits. DATA SYNTHESIS: We recommend 1) for asymptomatic patients, observation and consideration of decontamination following a potentially toxic calcium channel blocker ingestion (1D); 2) as first-line therapies (prioritized based on desired effect), IV calcium (1D), high-dose insulin therapy (1D-2D), and norepinephrine and/or epinephrine (1D). We also suggest dobutamine or epinephrine in the presence of cardiogenic shock (2D) and atropine in the presence of symptomatic bradycardia or conduction disturbance (2D); 3) in patients refractory to the first-line treatments, we suggest incremental doses of high-dose insulin therapy if myocardial dysfunction is present (2D), IV lipid-emulsion therapy (2D), and using a pacemaker in the presence of unstable bradycardia or…

OBJECTIVE: Early mobility in mechanically ventilated patients is safe, feasible, and may improve functional outcomes. We sought to determine the prevalence and character of mobility for ICU patients with acute respiratory failure in U.S. ICUs. DESIGN: Two-day cross-sectional point prevalence study. SETTING: Forty-two ICUs across 17 Acute Respiratory Distress Syndrome Network hospitals. PATIENTS: Adult patients (≥ 18 yr old) with acute respiratory failure requiring mechanical ventilation. INTERVENTIONS: We defined therapist-provided mobility as the proportion of patient-days with any physical or occupational therapy-provided mobility event. Hierarchical regression models were used to identify predictors of out-of-bed mobility. MEASUREMENTS AND MAIN RESULTS: Hospitals contributed 770 patient-days of data. Patients received mechanical ventilation on 73% of the patient-days mostly (n = 432; 56%) ventilated via an endotracheal tube. The prevalence of physical therapy/occupational therapy-provided mobility was 32% (247/770), with a significantly higher proportion of nonmechanically…

OBJECTIVE: To identify and measure recently described chemical mediators, termed specialized pro-resolving mediators that actively regulate the resolution of acute-inflammation, and correlate measurements with clinical outcomes. DESIGN: Herein, deidentified plasma was collected from sepsis patients (n = 22 subjects) within 48 hours of admission to the ICU and on days 3 and 7 thereafter and subjected to lipid mediator profiling. SETTING: Brigham and Women's Hospital Medical Intensive Care Unit. SUBJECTS: Patients in the medical ICU with sepsis. MEASUREMENTS AND MAIN RESULTS: In all patients, we identified more than 30 bioactive mediators and pathway markers in peripheral blood using established criteria for arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid metabolomes. These included inflammation initiating mediators leukotriene B4 and prostaglandin E2 and pro-resolving mediators resolvin D1, resolvin D2, and protectin D1. In sepsis nonsurvivors, we found significantly higher inflammation-initiating mediators including prostaglandin F2α and leukotriene B4 and…

OBJECTIVES: We recently described how spontaneous effort during mechanical ventilation can cause "pendelluft," that is, displacement of gas from nondependent (more recruited) lung to dependent (less recruited) lung during early inspiration. Such transfer depends on the coexistence of more recruited (source) liquid-like lung regions together with less recruited (target) solid-like lung regions. Pendelluft may improve gas exchange, but because of tidal recruitment, it may also contribute to injury. We hypothesize that higher positive end-expiratory pressure levels decrease the propensity to pendelluft and that with lower positive end-expiratory pressure levels, pendelluft is associated with improved gas exchange but increased tidal recruitment. DESIGN: Crossover design. SETTING: University animal research laboratory. SUBJECTS: Anesthetized landrace pigs. INTERVENTIONS: Surfactant depletion was achieved by saline lavage in anesthetized pigs, and ventilator-induced lung injury was produced by ventilation with high tidal volume and low positive end-expiratory pressure. Ventilation was…

OBJECTIVES: The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. DESIGN: Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. SETTING: One hundred twenty-eight PICUs in 26 countries. PATIENTS: Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred two…

OBJECTIVE: To determine the costs associated with delirium in critically ill children. DESIGN: Prospective observational study. SETTING: An urban, academic, tertiary-care PICU in New York city. PATIENTS: Four-hundred and sixty-four consecutive PICU admissions between September 2, 2014, and December 12, 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All children were assessed for delirium daily throughout their PICU stay. Hospital costs were analyzed using cost-to-charge ratios, in 2014 dollars. Median total PICU costs were higher in patients with delirium than in patients who were never delirious ($18,832 vs $4,803; p < 0.0001). Costs increased incrementally with number of days spent delirious (median cost of $9,173 for 1 d with delirium, $19,682 for 2-3 d with delirium, and $75,833 for > 3 d with delirium; p < 0.0001); this remained highly significant even after adjusting for PICU length of stay (p < 0.0001). After controlling for age, gender, severity of illness, and PICU length of stay, delirium was associated with an 85% increase in PICU costs (p < 0.0001).…

OBJECTIVE: To determine the influence of admission anthropometry on clinical outcomes in mechanically ventilated children in the PICU. DESIGN: Data from two multicenter cohort studies were compiled to examine the unique contribution of nutritional status, defined by body mass index z score, to 60-day mortality, hospital-acquired infections, length of hospital stay, and ventilator-free days, using multivariate analysis. SETTING: Ninety PICUs from 16 countries with eight or more beds. PATIENTS: Children aged 1 month to 18 years, admitted to each participating PICU and requiring mechanical ventilation for more than 48 hours. MEASUREMENTS AND MAIN RESULTS: Data from 1,622 eligible patients, 54.8% men and mean (SD) age 4.5 years (5.1), were analyzed. Subjects were classified as underweight (17.9%), normal weight (54.2%), overweight (14.5%), and obese (13.4%) based on body mass index z score at admission. After adjusting for severity of illness and site, the odds of 60-day mortality were higher in underweight (odds ratio, 1.53; p < 0.001) children. The odds of hospital-acquired infections…

OBJECTIVE: A systematic review and meta-analysis to assess the efficacy of earplugs as an ICU strategy for reducing delirium. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of controlled trials were searched using the terms "intensive care," "critical care," "earplugs," "sleep," "sleep disorders," and "delirium." STUDY SELECTION: Intervention studies (randomized or nonrandomized) assessing the efficacy of earplugs as a sleep hygiene strategy in patients admitted to a critical care environment were included. Studies were excluded if they included only healthy volunteers, did not report any outcomes of interest, did not contain an intervention group of interest, were crossover studies, or were only published in abstract form. DATA EXTRACTION: Nine studies published between 2009 and 2015, including 1,455 participants, fulfilled the eligibility criteria and were included in the systematic review. Studies included earplugs as an isolated intervention (n = 3), or as part of a bundle with eye shades (n = 2), or earplugs, eye shades, and additional sleep noise abatement…

Although sepsis was described more than 2,000 years ago, and clinicians still struggle to define it, there is no "gold standard," and multiple competing approaches and terms exist. Challenges include the ever-changing knowledge base that informs our understanding of sepsis, competing views on which aspects of any potential definition are most important, and the tendency of most potential criteria to be distributed in at-risk populations in such a way as to hinder separation into discrete sets of patients. We propose that the development and evaluation of any definition or diagnostic criteria should follow four steps: 1) define the epistemologic underpinning, 2) agree on all relevant terms used to frame the exercise, 3) state the intended purpose for any proposed set of criteria, and 4) adopt a scientific approach to inform on their usefulness with regard to the intended purpose. Usefulness can be measured across six domains: 1) reliability (stability of criteria during retesting, between raters, over time, and across settings), 2) content validity (similar to face validity), 3)…

OBJECTIVE: Lungs behave as viscoelastic polymers. Harms of mechanical ventilation could then depend on not only amplitude (strain) but also velocity (strain rate) of lung deformation. Herein, we tested this hypothesis. DESIGN: Laboratory investigation. SETTING: Animal unit. SUBJECTS: Thirty healthy piglets. INTERVENTIONS: Two groups of animals were ventilated for 54 hours with matched lung strains (ratio between tidal volume and functional residual capacity) but different lung strain rates (ratio between strain and inspiratory time). Individual strains ranged between 0.6 and 3.5 in both groups. Piglets ventilated with low strain rates had an inspiratory-to-expiratory time ratio of 1:2-1:3. Those ventilated with high strain rates had much lower inspiratory-to-expiratory time ratios (down to 1:9). Respiratory rate was always 15 breaths/min. Lung viscoelastic behavior, with ventilator setting required per protocol, was "quantified" as dynamic respiratory system hysteresis (pressure-volume loop [in Joules]) and stress relaxation (airway pressure drop during an end-inspiratory pause [in…

OBJECTIVES: The role of intraaortic balloon pumping combined with venoarterial extracorporeal membrane oxygenation in cardiogenic shock patients remains unknown. This study investigated the effect of intraaortic balloon pumping combined with venoarterial extracorporeal membrane oxygenation on reducing mortality of cardiogenic shock patients. DESIGN: Retrospective cohort study. SETTING: The Japanese Diagnosis Procedure Combination national inpatient database. PATIENTS: Cardiogenic shock adult patients receiving peripheral venoarterial extracorporeal membrane oxygenation at admission were identified in the Japanese Diagnosis Procedure Combination database from July 1, 2010, to March 31, 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were all-cause 28-day mortality and in-hospital mortality, and the secondary outcome was the proportion of patients weaned from venoarterial extracorporeal membrane oxygenation, using propensity score matching. Eligible patients (n = 1,650) were divided into the intraaortic balloon pumping combined with venoarterial…

OBJECTIVE: To determine the impact of adjuvant corticosteroids administered to patients hospitalized with influenza A (H7N9) viral pneumonia. DESIGN: The effects of adjuvant corticosteroids on mortality were assessed using multivariate Cox regression and a propensity score-matched case-control study. Nosocomial infections and viral shedding were also compared. SETTING: Hospitals with influenza A (H7N9) viral pneumonia patient admission in 84 cities and 16 provinces of Mainland China. PATIENTS: Adolescent and Adult patients aged >14 yr with severe laboratory-confirmed influenza A (H7N9) virus infections were screened from April 2013 to March 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study population comprised 288 cases who were hospitalized with influenza A (H7N9) viral pneumonia. The median age of the study population was 58 years, 69.8% of the cohort comprised male patients, and 51.4% had at least one type of underlying diseases. The in-hospital mortality was 31.9%. Two hundred and four patients (70.8%) received adjuvant corticosteroids; among them, 193 had…

OBJECTIVE: To investigate whether the collapsibility index of the inferior vena cava recorded during a deep standardized inspiration predicts fluid responsiveness in nonintubated patients. DESIGN: Prospective, nonrandomized study. SETTING: ICUs at a general and a university hospital. PATIENTS: Nonintubated patients without mechanical ventilation (n = 90) presenting with sepsis-induced acute circulatory failure and considered for volume expansion. INTERVENTIONS: We assessed hemodynamic status at baseline and after a volume expansion induced by a 30-minute infusion of 500-mL gelatin 4%. MEASUREMENTS AND MAIN RESULTS: We measured stroke volume index and collapsibility index of the inferior vena cava under a deep standardized inspiration using transthoracic echocardiography. Vena cava pertinent diameters were measured 15-20 mm caudal to the hepatic vein junction and recorded by bidimensional imaging on a subcostal long-axis view. Standardized respiratory cycles consisted of a deep standardized inspiration followed by passive exhalation. The collapsibility index expressed in percentage…

OBJECTIVE: To evaluate prevalence, severity, and co-occurrence of and risk factors for depression, anxiety, and posttraumatic stress disorder symptoms over the first year after acute respiratory distress syndrome. DESIGN: Prospective longitudinal cohort study. SETTINGS: Forty-one Acute Respiratory Distress Syndrome Network hospitals across the United States. PATIENTS: Six hundred ninety-eight acute respiratory distress syndrome survivors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Psychiatric symptoms were evaluated by using the Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised at 6 and 12 months. Adjusted prevalence ratios for substantial symptoms (binary outcome) and severity scores were calculated by using Poisson and linear regression, respectively. During 12 months, a total of 416 of 629 patients (66%) with at least one psychiatric outcome measure had substantial symptoms in at least one domain. There was a high and almost identical prevalence of substantial symptoms (36%, 42%, and 24% for depression, anxiety, and posttraumatic stress disorder) at…

OBJECTIVE: Mechanical ventilation contributes to diaphragmatic atrophy and dysfunction, and few techniques exist to assess diaphragmatic function: the purpose of this study was to quantify diaphragm atrophy in a population of critically ill mechanically ventilated patients with ultrasound and to identify risk factors that can worsen diaphragmatic activity. DESIGN: Prospective observational study. SETTING: ICU of a 1,200-bed university hospital. PATIENTS: Newly intubated adult critically ill patients. INTERVENTIONS: Diaphragm thickness in the zone of apposition was measured daily with ultrasound, from the first day of mechanical ventilation till discharge to the main ward. MEASUREMENTS AND MAIN RESULTS: Daily atrophy rate (ΔTdi/d) was calculated as the reduction in percentage from the previous measurement. To analyze the difference in atrophy rate (ΔTdi/d), ventilation was categorized into four classes: spontaneous breathing or continuous positive airway pressure; pressure support ventilation 5-12 cm H2O (low pressure support ventilation); pressure support ventilation greater than 12…

OBJECTIVES: During critical illness, impaired endothelial vascular reactivity predicts prolonged acute brain dysfunction, but relationships between endothelial activation, blood-brain barrier/neurological injury, and acute brain dysfunction, including delirium, remain unexamined. We tested the hypothesis that elevated plasma markers of endothelial activation and blood-brain barrier/neurological injury are associated with delirium duration during critical illness. DESIGN: Prospective cohort study. SETTING: Medical and surgical ICUs in an academic medical center. PATIENTS: Adults in acute respiratory failure and/or shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We enrolled subjects within 72 hours of organ failure diagnosis in the ICU. We measured plasma concentrations of plasminogen activator inhibitor-1, E-selectin, and angiopoietin-2 as markers of endothelial activation and S100B as a marker of blood-brain barrier/neurological injury in blood collected at enrollment. We assessed patients for delirium and coma twice daily after enrollment using the Confusion Assessment…

OBJECTIVE: Incident acute kidney injury and prevalent chronic kidney disease are commonly encountered in septic patients. We examined the differential effect of acute kidney injury and chronic kidney disease on the association between cumulative fluid balance and hospital mortality in critically ill septic patients. DESIGN: Retrospective cohort study. SETTING: Urban academic medical center ICU. PATIENTS: ICU adult patients with severe sepsis or septic shock and serum creatinine measured within 3 months prior to and 72 hours of ICU admission. Patients with estimated glomerular filtration rate less than 15 mL/min/1.73 m or receiving chronic dialysis were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 2,632 patients, 1,211 with chronic kidney disease, were followed up until hospital death or discharge. Acute kidney injury occurred in 1,525 patients (57.9%), of whom 679 (44.5%) had chronic kidney disease. Hospital mortality occurred in 603 patients (22.9%). Every 1-L increase in cumulative fluid balance at 72 hours of ICU admission was independently associated…

OBJECTIVES: Prognostic and predictive enrichment strategies are fundamental tools of precision medicine. Identifying children with septic shock who may benefit from corticosteroids remains a challenge. We combined prognostic and predictive strategies to identify a pediatric septic shock subgroup responsive to corticosteroids. DESIGN: We conducted a secondary analysis of 288 previously published pediatric subjects with septic shock. For prognostic enrichment, each study subject was assigned a baseline mortality probability using the pediatric sepsis biomarker risk model. For predictive enrichment, each study subject was allocated to one of two septic shock endotypes, based on a 100-gene signature reflecting adaptive immunity and glucocorticoid receptor signaling. The primary study endpoint was complicated course, defined as the persistence of two or more organ failures at day 7 of septic shock or 28-day mortality. We used logistic regression to test for an association between corticosteroids and complicated course within endotype. MEASUREMENTS AND MAIN RESULTS: Among endotype B…

Ahmed, Wael MD; Fowler, Robert A. MDCM, MS (Epi); McCredie, Victoria A. MBChB, PhD (can) Author Information

OBJECTIVE: The Pediatric Sepsis Biomarker Risk Model (PERSEVERE), a pediatric sepsis risk model, uses biomarkers to estimate baseline mortality risk for pediatric septic shock. It is unknown how PERSEVERE performs within distinct septic shock phenotypes. We tested PERSEVERE in children with septic shock and thrombocytopenia-associated multiple organ failure (TAMOF), and in those without new onset thrombocytopenia but with multiple organ failure (MOF). DESIGN: PERSEVERE-based mortality risk was generated for each study subject (n = 660). A priori, we determined that if PERSEVERE did not perform well in both the TAMOF and the MOF cohorts, we would revise PERSEVERE to incorporate admission platelet counts. SETTING: Multiple PICUs in the United States. INTERVENTIONS: Standard care. MEASUREMENTS AND MAIN RESULTS: PERSEVERE performed well in the TAMOF cohort (areas under the receiver operating characteristic curves [AUC], 0.84 [95% CI, 0.77-0.90]), but less well in the MOF cohort (AUC, 0.71 [0.61-0.80]). PERSEVERE was revised using 424 subjects previously reported in the derivation phase.…

OBJECTIVES: To characterize survivors' employment status after critical illness and to determine if duration of delirium during hospitalization and residual cognitive function are each independently associated with decreased employment. DESIGN: Prospective cohort investigation with baseline and in-hospital clinical data and follow-up at 3 and 12 months. SETTING: Medical and surgical ICUs at two tertiary-care hospitals. PATIENTS: Previously employed patients from the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors study who survived a critical illness due to respiratory failure or shock were evaluated for global cognition and employment status at 3- and 12-month follow-up. MEASUREMENTS AND MAIN RESULTS: We used multivariable logistic regression to evaluate independent associations between employment at both 3 and 12 months and global cognitive function at the same time point, and delirium during the hospital stay. At 3-month follow-up, 113 of the total survival cohort of 448 (25%) were identified as being employed at study…

OBJECTIVES: Currently used biomarkers insufficiently discriminate between patients with systemic inflammatory response syndrome of non-infectious origin and sepsis. The aim of this study was to identify surrogate markers that distinguish between systemic inflammatory response syndrome and sepsis as well as the underlying type of infection by targeted metabolomics. DESIGN: Retrospective analysis. SETTINGS: Six sites of the Hellenic Sepsis Study Group and at Jena University Hospital. PATIENTS: A total of 406 patients were analyzed: 66 fulfilling criteria for diagnosis of systemic inflammatory response syndrome, 100 for community-acquired pneumonia, 112 for urinary tract infection, 83 for intra-abdominal infection and 45 for bloodstream infection. Patients were divided into test cohort (n = 268) and confirmation cohort (n = 138). INTERVENTIONS: A total of 186 metabolites were determined by liquid chromatography tandem mass spectrometry. MEASUREMENTS AND MAIN RESULTS: Serum concentrations of most acylcarnitines, glycerophospholipids and sphingolipids were altered in sepsis compared to…

OBJECTIVES: To investigate whether admission hyperglycemia is associated with the presentation and/or outcome of sepsis, what the influence of hyperglycemia is on key host responses to sepsis, and whether hyperglycemia differentially affects patients with diabetes mellitus. DESIGN AND SETTING: A substudy of a prospective observational cohort study was conducted in the intensive care of two tertiary hospitals between January 2011 and July 2013. PATIENTS: Of all consecutive critically ill sepsis patients, admission glucose was used to stratify patients in euglycemia (71-140 mg/dL), mild hyperglycemia (141-199 mg/dL), and severe hyperglycemia (≥ 200 mg/dL), and patients with hypoglycemia were excluded. Fifteen plasma biomarkers providing insight in key host responses implicated in sepsis pathogenesis were measured on admission. MEASUREMENTS AND MAIN RESULTS: Of 987 sepsis patients with admission glucose levels greater than 70 mg/dL, 519 (52.6%) had normal glucose levels, 267 (27.1%) had mild, and 201 (20.4%) severe hyperglycemia. Admission hyperglycemia was accompanied by mitigated…

PRELIMINARY REMARKS Guideline Limitations Practice guidelines should be used in the context of individual patient characteristics and may be superseded by clinical judgment or patient preference. The use of practice guidelines does not guarantee specific outcome benefit but rather should serve as an evidence-based tool for clinicians. This guideline addresses commonly encountered antithrombotic-associated intracranial hemorrhage scenarios for which data and experience have been reported. Management of patients with complex situations (e.g., intracerebral hemorrhage with intrinsic coagulopathy, thrombocytopenia, disseminated intravascular coagulopathy [DIC], polytrauma, and/or concomitant ischemia or thrombophilia) will require prioritizing interventions and risk-benefit analyses. For these situations, the information here should serve as a first guide, with reliance upon local and outside experts in a multidisciplinary team to help formulate treatment plans where necessary. This guideline did not specifically address antithrombotic reversal in a pediatric population. For some…

OBJECTIVES: To determine mortality and costs associated with adherence to an aggressive, 3-hour sepsis bundle versus noncompliance with greater than or equal to one bundle element for severe sepsis and septic shock patients. DESIGN: Prospective, multisite, observational study following three sequential, independent cohorts, from a single U.S. health system, through their hospitalization. SETTING: Cohort 1: five tertiary and six community hospitals. Cohort 2: single tertiary, academic medical center. Cohort 3: five tertiary and four community hospitals. PATIENTS: Consecutive sample of all severe sepsis and septic shock patients (defined: infection, ≥ 2 systemic inflammatory response syndrome, and hypoperfusive organ dysfunction) identified by a quality initiative. The exposure was full 3-hour bundle compliance. Bundle elements are as follows: 1) blood cultures before antibiotics; 2) parenteral antibiotics administered less than or equal to 180 minutes from greater than or equal to two systemic inflammatory response syndrome "and" lactate ordered, or less than or equal to 60 minutes…

OBJECTIVE: The objectives of this study are to determine what is the minimal volume required to perform an effective fluid challenge and to investigate how different doses of IV fluids in an fluid challenge affect the changes in cardiac output and the proportion of responders and nonresponders. DESIGN: Quasi-randomized controlled trial. SETTING: Cardiothoracic ICU, tertiary university hospital. PATIENTS: Eighty postcardiac surgery patients. INTERVENTION: IV infusion of 1, 2, 3, or 4 mL/Kg (body weight) of crystalloid over 5 minutes. MEASUREMENTS AND MAIN RESULTS: Mean systemic filling pressure measured using the transient stop-flow arm arterial-venous equilibrium pressure, arterial and central venous pressure, cardiac output (LiDCOplus; LiDCO, Cambridge, United Kingdom), and heart rate. The groups were well matched with respect to demographic and baseline physiologic variables. The proportion of responders increased from 20% in the group of 1 mL/kg to 65% in the group of 4 mL/kg (p = 0.04). The predicted minimal volume required for an fluid challenge was between 321 and 509 mL. Only…

OBJECTIVE: Volutrauma and atelectrauma promote ventilator-induced lung injury, but their relative contribution to inflammation in ventilator-induced lung injury is not well established. The aim of this study was to determine the impact of volutrauma and atelectrauma on the distribution of lung inflammation in experimental acute respiratory distress syndrome. DESIGN: Laboratory investigation. SETTING: University-hospital research facility. SUBJECTS: Ten pigs (five per group; 34.7-49.9 kg) INTERVENTIONS: : Animals were anesthetized and intubated, and saline lung lavage was performed. Lungs were separated with a double-lumen tube. Following lung recruitment and decremental positive end-expiratory pressure trial, animals were randomly assigned to 4 hours of ventilation of the left (ventilator-induced lung injury) lung with tidal volume of approximately 3 mL/kg and 1) high positive end-expiratory pressure set above the level where dynamic compliance increased more than 5% during positive end-expiratory pressure trial (volutrauma); or 2) low positive end-expiratory pressure to achieve…

OBJECTIVE: To evaluate the effect of video laryngoscopy on the rate of endotracheal intubation on first laryngoscopy attempt among critically ill adults. DESIGN: A randomized, parallel-group, pragmatic trial of video compared with direct laryngoscopy for 150 adults undergoing endotracheal intubation by Pulmonary and Critical Care Medicine fellows. SETTING: Medical ICU in a tertiary, academic medical center. PATIENTS: Critically ill patients 18 years old or older. INTERVENTIONS: Patients were randomized 1:1 to video or direct laryngoscopy for the first attempt at endotracheal intubation. MEASUREMENTS AND MAIN RESULTS: Patients assigned to video (n = 74) and direct (n = 76) laryngoscopy were similar at baseline. Despite better glottic visualization with video laryngoscopy, there was no difference in the primary outcome of intubation on the first laryngoscopy attempt (video 68.9% vs direct 65.8%; p = 0.68) in unadjusted analyses or after adjustment for the operator's previous experience with the assigned device (odds ratio for video laryngoscopy on intubation on first attempt 2.02; 95%…

OBJECTIVE: Because iron is both an essential and toxic micronutrient influencing the development of microbial infections, we evaluated the usefulness of iron parameters as outcome predictors in ICU patients. DESIGN: Prospective clinical single-center non-interventional study. SETTING: General internal medicine ICU; German University hospital. PATIENTS: One hundred and twelve septic and 43 nonseptic ICU patients, 156 healthy blood donors. MEASUREMENTS AND MAIN RESULTS: Serum iron parameters at admission were correlated with short and long term mortality in ICU subjects. Both hepcidin and ferritin concentrations were significantly elevated in ICU patients compared with blood donors and were the highest in septic patients. On the contrary, serum iron and transferrin levels were decreased in ICU subjects with lowest values among septic patients. Hepcidin values correlated with ferritin levels, and serum iron correlated strongly with transferrin saturation. A moderate correlation of hepcidin, ferritin, and transferrin with inflammatory parameters was noted. Both short- and long-term…

OBJECTIVES: To examine the performance of the urinary biomarker panel tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in patients with sepsis at ICU admission. To investigate the effect of nonrenal organ dysfunction on tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 in this population. METHOD: In this ancillary analysis, we included patients with sepsis who were enrolled in either of two trials including 39 ICUs across Europe and North America. The primary endpoint was moderate-severe acute kidney injury (equivalent to Kidney Disease Improving Global Outcome stage 2-3) within 12 hours of enrollment. We assessed biomarker performance by calculating the area under the receiver operating characteristic curve, sensitivity, specificity, and negative and positive predictive values at three cutoffs: 0.3, 1.0, and 2.0 (ng/mL)/1,000. We also calculated nonrenal Sequential Organ Failure Assessment scores for each patient on enrollment and compared tissue inhibitor of metalloproteinase-2 and insulin-like growth…

OBJECTIVES: Cardiac arrest is associated with morbidity and mortality because of cerebral ischemia. Therefore, we tested the hypothesis that higher regional cerebral oxygenation during resuscitation is associated with improved return of spontaneous circulation, survival, and neurologic outcomes at hospital discharge. We further examined the validity of regional cerebral oxygenation as a test to predict these outcomes. DESIGN: Multicenter prospective study of in-hospital cardiac arrest. SETTING: Five medical centers in the United States and the United Kingdom. PATIENTS: Inclusion criteria are as follows: in-hospital cardiac arrest, age 18 years old or older, and prolonged cardiopulmonary resuscitation greater than or equal to 5 minutes. Patients were recruited consecutively during working hours between August 2011 and September 2014. Survival with a favorable neurologic outcome was defined as a cerebral performance category 1-2. INTERVENTIONS: Cerebral oximetry monitoring. MEASUREMENTS AND MAIN RESULTS: Among 504 in-hospital cardiac arrest events, 183 (36%) met inclusion criteria.…

OBJECTIVES: Perceiving nonbeneficial treatment is stressful for ICU staff and may be associated with burnout. We aimed to investigate predictors and consequences of perceived nonbeneficial treatment and to compare nurses and junior and senior physicians. DESIGN: Cross-sectional, multicenter paper-pencil survey on personal and work-related characteristics, perceived nonbeneficial treatment, burnout, and intention to leave the job. SETTING: Convenience sample of 23 German ICUs. SUBJECTS: ICU nurses and physicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 847 questionnaires were returned (51% response); 778 had complete data for final multivariate analyses. Nonbeneficial treatment was in median perceived "sometimes." Adjusted for covariates, it was perceived more often by nurses and junior physicians (both p ≤ 0.001 in comparison to senior physicians), while emotional exhaustion was highest in junior physicians (p ≤ 0.015 in comparison to senior physicians and nurses), who also had a higher intention to leave than nurses (p = 0.024). Nonbeneficial treatment was…

OBJECTIVES: To evaluate the internal consistency, validity, responsiveness, and minimal important difference of the Functional Status Score for the ICU, a physical function measure designed for the ICU. DESIGN: Clinimetric analysis. SETTINGS: Five international datasets from the United States, Australia, and Brazil. PATIENTS: Eight hundred nineteen ICU patients. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Clinimetric analyses were initially conducted separately for each data source and time point to examine generalizability of findings, with pooled analyses performed thereafter to increase power of analyses. The Functional Status Score for the ICU demonstrated good to excellent internal consistency. There was good convergent and discriminant validity, with significant and positive correlations (r = 0.30-0.95) between Functional Status Score for the ICU and other physical function measures, and generally weaker correlations with nonphysical measures (|r| = 0.01-0.70). Known group validity was demonstrated by significantly higher Functional Status Score for the ICU scores among…

OBJECTIVES: To evaluate the clinical effectiveness, safety, and cost of dexmedetomidine for the treatment of agitated delirium refractory to haloperidol in nonintubated critically ill patients. DESIGN: Nonrandomized, controlled trial. SETTING: Intensive care department of a tertiary care nonprofit hospital. PATIENTS: All consecutive admissions to a medical-surgical ICU with a diagnosis of agitated delirium. INTERVENTIONS: Initial haloperidol titration: all patients received IV bolus doses of haloperidol until agitation was controlled (Richmond Agitation Sedation Scale scoring range, 0 to -2) or reaching the maximum daily dose. Group comparison: patient responders to haloperidol (control group) were compared with nonresponders (dexmedetomidine group). MEASUREMENTS AND MAIN RESULTS: A total of 132 nonintubated patients were treated with haloperidol in the initial haloperidol titration phase. Forty-six patients (34.8%; 95% CI, 26.0-43.1%) did not respond to haloperidol, and 86 patients (65.2%; 95% CI, 56.3-73.0%) were responders. During the group comparison phase, dexmedetomidine…

OBJECTIVE: We performed a systematic review and meta-analysis to examine the accuracy of bedside ultrasound for confirmation of central venous catheter position and exclusion of pneumothorax compared with chest radiography. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, reference lists, conference proceedings and ClinicalTrials.gov. STUDY SELECTION: Articles and abstracts describing the diagnostic accuracy of bedside ultrasound compared with chest radiography for confirmation of central venous catheters in sufficient detail to reconstruct 2 × 2 contingency tables were reviewed. Primary outcomes included the accuracy of confirming catheter positioning and detecting a pneumothorax. Secondary outcomes included feasibility, interrater reliability, and efficiency to complete bedside ultrasound confirmation of central venous catheter position. DATA EXTRACTION: Investigators abstracted study details including research design and sonographic imaging technique to detect catheter malposition and procedure-related pneumothorax. Diagnostic accuracy measures…

OBJECTIVES: Changes in population demographics and comorbid illness prevalence, improvements in medical care, and shifts in care delivery may be driving changes in the composition of patients admitted to the ICU. We sought to describe the changing demographics, diagnoses, and outcomes of patients admitted to critical care units in the U.S. hospitals. DESIGN: Retrospective cohort study. SETTING: U.S. hospitals. PATIENTS: There were 27.8 million elderly (age, > 64 yr) fee-for-service Medicare beneficiaries hospitalized with an intensive care or coronary care room and board charge from 1996 to 2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We aggregated primary International Classification of Diseases, 9th Revision, Clinical Modification discharge diagnosis codes into diagnoses and disease categories. We examined trends in demographics, primary diagnosis, and outcomes among patients with critical care stays. Between 1996 and 2010, we found significant declines in patients with a primary diagnosis of cardiovascular disease, including coronary artery disease (26.6 to 12.6% of…

OBJECTIVES: A cuffed tracheostomy tube facilitates prolonged mechanical ventilation and weaning but usually leads to prolonged voicelessness, which can be one of the most negative experiences of hospitalization. No randomized trials have examined the effects of targeted early communication intervention for the restoration of voice in ventilated tracheostomy patients in the ICU. DESIGN: A prospective randomized clinical trial. SETTING: The trial was conducted in the ICU of an urban tertiary level hospital. PATIENTS: Thirty adult participants enrolled, with 15 randomly allocated to the intervention and control groups. INTERVENTIONS: The early intervention group received early cuff deflation and insertion of an in-line speaking valve during mechanical ventilation. The control group received standard cuff deflation and a speaking valve during self-ventilation. A speech-language pathologist provided all treatments. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was time from tracheostomy insertion to phonation. Early intervention significantly hastened return to phonation…

OBJECTIVE: Low tidal volume ventilation lowers mortality in the acute respiratory distress syndrome. Previous studies reported poor low tidal volume ventilation implementation. We sought to determine the rate, quality, and predictors of low tidal volume ventilation use. DESIGN: Retrospective cross-sectional study. SETTING: One academic and three community hospitals in the Chicago region. PATIENTS: A total of 362 adults meeting the Berlin Definition of acute respiratory distress syndrome consecutively admitted between June and December 2013. MEASUREMENTS AND MAIN RESULTS: Seventy patients (19.3%) were treated with low tidal volume ventilation (tidal volume < 6.5 mL/kg predicted body weight) at some time during mechanical ventilation. In total, 22.2% of patients requiring an FIO2 greater than 40% and 37.3% of patients with FIO2 greater than 40% and plateau pressure greater than 30 cm H2O received low tidal volume ventilation. The entire cohort received low tidal volume ventilation 11.4% of the time patients had acute respiratory distress syndrome. Among patients who received low tidal…

OBJECTIVES: Pantoprazole is frequently administered to critically ill patients for prophylaxis against gastrointestinal bleeding. However, comparison to placebo has been inadequately evaluated, and pantoprazole has the potential to cause harm. Our objective was to evaluate benefit or harm associated with pantoprazole administration. DESIGN: Prospective randomized double-blind parallel-group study. SETTING: University-affiliated mixed medical-surgical ICU. PATIENTS: Mechanically ventilated critically ill patients suitable for enteral nutrition. INTERVENTIONS: We randomly assigned patients to receive either daily IV placebo or pantoprazole. MEASUREMENTS AND MAIN RESULTS: Major outcomes were clinically significant gastrointestinal bleeding, infective ventilator-associated complication or pneumonia, and Clostridium difficile infection; minor outcomes included overt bleeding, hemoglobin concentration profiles, and mortality. None of the 214 patients randomized had an episode of clinically significant gastrointestinal bleeding, three patients met the criteria for either an infective…

OBJECTIVE: High-flow nasal cannulae are used in adults with or at risk of acute respiratory failure. We conducted a systematic review and meta-analysis to evaluate the evidence for their use in this setting. DATA SOURCES: Ovid Medline, Embase, and Cochrane Database of Systematic Reviews. STUDY SELECTION: Databases were searched for randomized controlled trials comparing administration of high-flow nasal cannulae with usual care (i.e., conventional oxygen therapy or noninvasive ventilation) in adults with respiratory failure. The primary outcome was hospital mortality; the rate of intubation and assessment of delirium and comfort were secondary outcomes. DATA EXTRACTION: One hundred forty-seven nonduplicate citations were screened, 32 underwent full screening and data extraction, and 14 trials were eligible for inclusion in the review. Nine trials were used in the meta-analysis, including a total of 2,507 subjects. DATA SYNTHESIS: When high-flow nasal cannulae were compared with usual care, there was no difference in mortality (high-flow nasal cannulae, 60/1,006 [6%] vs usual care,…

OBJECTIVE: We sought to investigate if the chloride content of fluids used in resuscitation was associated with short- and long-term outcomes. DESIGN: We identified patients who received large-volume fluid resuscitation, defined as greater than 60 mL/kg over a 24-hour period. Chloride load was determined for each patient based on the chloride ion concentration of the fluids they received during large-volume fluid resuscitation multiplied by the volume of fluids. We compared the development of hyperchloremic acidosis, acute kidney injury, and survival among those with higher and lower chloride loads. SETTING: University Medical Center. PATIENTS: Patients admitted to ICUs from 2000 to 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 4,710 patients receiving large-volume fluid resuscitation, hyperchloremic acidosis was documented in 523 (11%). Crude rates of hyperchloremic acidosis, acute kidney injury, and hospital mortality all increased significantly as chloride load increased (p < 0.001). However, chloride load was no longer associated with hyperchloremic acidosis or…

OBJECTIVE: We propose a novel paradigm to predict acute attacks and exacerbations in chronic episodic disorders such as asthma, cardiac arrhythmias, migraine, epilepsy, and depression. A better generic understanding of acute transitions in chronic dynamic diseases is increasingly important in critical care medicine because of the higher prevalence and incidence of these chronic diseases in our aging societies. DATA SOURCES: PubMed, Medline, and Web of Science. STUDY SELECTION: We selected studies from biology and medicine providing evidence of slowing down after a perturbation as a warning signal for critical transitions. DATA EXTRACTION: Recent work in ecology, climate, and systems biology has shown that slowing down of recovery upon perturbations can indicate loss of resilience across complex, nonlinear biologic systems that are approaching a tipping point. This observation is supported by the empiric studies in pathophysiology and controlled laboratory experiments with other living systems, which can flip from one state of clinical balance to a contrasting one. We discuss…

OBJECTIVE: The relationship between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness remains unclear. We examined the association between neuromuscular blocking agents and ICU-acquired weakness, critical illness polyneuropathy, and critical illness myopathy. DATA SOURCES: PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and bibliographies of included studies were searched from database inception until September 24, 2015. STUDY SELECTION: Randomized controlled trials and prospective observational studies examining the association between neuromuscular blocking agents and ICU-acquired weakness, critical illness polyneuropathy, or critical illness myopathy. DATA EXTRACTION: One author screened titles/abstracts. Two authors independently reviewed full text and extracted data from included studies. Meta-analysis was performed using the DerSimonian-Laird random effects model (OpenMetaAnalyst 10.10 for OS.X). We assessed reporting bias with funnel plots and…

OBJECTIVES: To establish the effect of continuous renal replacement therapy on outcome in pediatric acute liver failure. DESIGN: Retrospective cohort study. SETTING: Sixteen-bed PICU in a university-affiliated tertiary care hospital and specialist liver centre. PATIENTS: All children (0-18 yr) admitted to PICU with pediatric acute liver failure between January 2003 and December 2013. INTERVENTIONS: Children with pediatric acute liver failure were managed according to a set protocol. The guidelines for continuous renal replacement therapy in pediatric acute liver failure were changed in 2011 following preliminary results to indicate the earlier use of continuous renal replacement therapy for both renal dysfunction and detoxification. MEASUREMENTS AND MAIN RESULTS: Of 165 children admitted with pediatric acute liver failure, 136 met the inclusion criteria and 45 of these received continuous renal replacement therapy prior to transplantation or recovery. Of the children managed with continuous renal replacement therapy, 26 (58%) survived: 19 were successfully bridged to liver…

OBJECTIVES: Heterogeneity in sepsis-related pathobiology presents a significant challenge. Resolving this heterogeneity presents an opportunity to understand pathobiology and improve patient care. Olfactomedin-4 is a neutrophil subset marker and may contribute to sepsis heterogeneity. Our objective was to evaluate the expression of olfactomedin-4 and characterize neutrophil heterogeneity in children with septic shock. DESIGN: Single-center, prospective cohort, as well as secondary analysis of existing transcriptomic and proteomic databases. SETTING: Tertiary care PICU. PATIENTS: Patients from 5 days to 18 years old with septic shock were enrolled. Data collected included the expression of olfactomedin-4 messenger RNA, serum protein concentrations, and percentage of neutrophils that express olfactomedin-4. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Secondary analysis of existing transcriptomic data demonstrated that olfactomedin-4 is the most highly expressed gene in nonsurvivors of pediatric septic shock, compared with survivors. Secondary analysis of an existing proteomic…

BACKGROUND: Selection of central venous catheter insertion site in ICU patients could help reduce catheter-related infections. Although subclavian was considered the most appropriate site, its preferential use in ICU patients is not generalized and questioned by contradicted meta-analysis results. In addition, conflicting data exist on alternative site selection whenever subclavian is contraindicated. OBJECTIVE: To compare catheter-related bloodstream infection and colonization risk between the three sites (subclavian, internal jugular, and femoral) in adult ICU patients. DATA SOURCE: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled trials, CINAHL, and ClinicalTrials.gov. STUDY SELECTION: Eligible studies were randomized controlled trials and observational ones. DATA EXTRACTION: Extracted data were analyzed by pairwise and network meta-analysis. DATA SYNTHESIS: Twenty studies were included; 11 were observational, seven were randomized controlled trials for other outcomes, and two were randomized controlled trials for sites. We evaluated 18,554 central venous…

OBJECTIVE: Addressing the quality gap in ICU-based palliative care is limited by uncertainty about acceptable models of collaborative specialist and generalist care. Therefore, we characterized the attitudes of physicians and nurses about palliative care delivery in an ICU environment. DESIGN: Mixed-methods study. SETTING: Medical and surgical ICUs at three large academic hospitals. PARTICIPANTS: Three hundred three nurses, intensivists, and advanced practice providers. MEASUREMENTS AND MAIN RESULTS: Clinicians completed written surveys that assessed attitudes about specialist palliative care presence and integration into the ICU setting, as well as acceptability of 23 published palliative care prompts (triggers) for specialist consultation. Most (n = 225; 75%) reported that palliative care consultation was underutilized. Prompting consideration of eligibility for specialist consultation by electronic health record searches for triggers was most preferred (n = 123; 41%); only 17 of them (6%) felt current processes were adequate. The most acceptable specialist triggers were…

OBJECTIVES: Although there is general agreement on the characteristic features of the acute respiratory distress syndrome, we lack a scoring system that predicts acute respiratory distress syndrome outcome with high probability. Our objective was to develop an outcome score that clinicians could easily calculate at the bedside to predict the risk of death of acute respiratory distress syndrome patients 24 hours after diagnosis. DESIGN: A prospective, multicenter, observational, descriptive, and validation study. SETTING: A network of multidisciplinary ICUs. PATIENTS: Six-hundred patients meeting Berlin criteria for moderate and severe acute respiratory distress syndrome enrolled in two independent cohorts treated with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using individual demographic, pulmonary, and systemic data at 24 hours after acute respiratory distress syndrome diagnosis, we derived our prediction score in 300 acute respiratory distress syndrome patients based on stratification of variable values into tertiles, and validated in an…

OBJECTIVE: We systematically reviewed models to predict adult ICU length of stay. DATA SOURCES: We searched the Ovid EMBASE and MEDLINE databases for studies on the development or validation of ICU length of stay prediction models. STUDY SELECTION: We identified 11 studies describing the development of 31 prediction models and three describing external validation of one of these models. DATA EXTRACTION: Clinicians use ICU length of stay predictions for planning ICU capacity, identifying unexpectedly long ICU length of stay, and benchmarking ICUs. We required the model variables to have been published and for the models to be free of organizational characteristics and to produce accurate predictions, as assessed by R across patients for planning and identifying unexpectedly long ICU length of stay and across ICUs for benchmarking, with low calibration bias. We assessed the reporting quality using the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies. DATA SYNTHESIS: The number of admissions ranged from 253 to 178,503. Median…

OBJECTIVES: Patients in ICUs are susceptible to subacute potentially catastrophic illnesses such as respiratory failure, sepsis, and hemorrhage that present as severe derangements of vital signs. More subtle physiologic signatures may be present before clinical deterioration, when treatment might be more effective. We performed multivariate statistical analyses of bedside physiologic monitoring data to identify such early subclinical signatures of incipient life-threatening illness. DESIGN: We report a study of model development and validation of a retrospective observational cohort using resampling (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis type 1b internal validation) and a study of model validation using separate data (type 2b internal/external validation). SETTING: University of Virginia Health System (Charlottesville), a tertiary-care, academic medical center. PATIENTS: Critically ill patients consecutively admitted between January 2009 and June 2015 to either the neonatal, surgical/trauma/burn, or medical ICUs with…

OBJECTIVES: Intracerebral hemorrhage is a devastating disorder with no current treatment. Whether perihematomal edema is an independent predictor of neurologic outcome is controversial. We sought to determine whether perihematomal edema expansion rate predicts outcome after intracerebral hemorrhage. DESIGN: Retrospective cohort study. SETTING: Tertiary medical center. PATIENTS: One hundred thirty-nine consecutive supratentorial spontaneous intracerebral hemorrhage patients 18 years or older admitted between 2000 and 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intracerebral hemorrhage, intraventricular hemorrhage, and perihematomal edema volumes were measured from CT scans obtained at presentation, 24-hours, and 72-hours postintracerebral hemorrhage. Perihematomal edema expansion rate was the difference between initial and follow-up perihematomal edema volumes divided by the time interval. Logistic regression was performed to evaluate the relationship between 1) perihematomal edema expansion rate at 24 hours and 90-day mortality and 2) perihematomal edema expansion rate…

OBJECTIVE: Treatment of viral fulminant myocarditis relies on life support measures. Based on studies pointing to a role for the proinflammatory cytokine interleukin-1 in myocardial inflammation and contractile dysfunction, we treated a patient with fulminant viral myocarditis with the interleukin-1 receptor blocking agent anakinra. We report the response and discuss the biologic rationale of this novel treatment approach. DESIGN: Case report. SETTING: ICU. PATIENT: A 36-year-old woman who was hospitalized for fulminant myocarditis with biventricular failure and cardiogenic shock, acutely manifested with hypotension and dyspnea. INTERVENTIONS: Following the progressive, life-threatening collapse of the cardiac function in spite of treatment with venous-arterial extracorporeal membrane oxygenation and mechanical circulatory support with a left ventricular assist device, treatment with the interleukin-1 receptor blocking agent anakinra 100 mg/d was started. MEASUREMENTS AND MAIN RESULTS: The severe depression of cardiac function responded promptly to interleukin-1 inhibition. Within 4…

OBJECTIVE: Therapeutic hypothermia has been used to attenuate the effects of traumatic brain injuries. However, the required degree of hypothermia, length of its use, and its timing are uncertain. We undertook a comprehensive meta-analysis to quantify benefits of hypothermia therapy for traumatic brain injuries in adults and children by analyzing mortality rates, neurologic outcomes, and adverse effects. DATA SOURCES: Electronic databases PubMed, Google Scholar, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov and manual searches of studies were conducted for relevant publications up until February 2016. STUDY SELECTION: Forty-one studies in adults (n = 3,109; age range, 18-81 yr) and eight studies in children (n = 454; age range, 3 mo to 18 yr) met eligibility criteria. DATA EXTRACTION: Baseline patient characteristics, enrollment time, methodology of cooling, target temperature, duration of hypothermia, and rewarming protocols were extracted. DATA SYNTHESIS: Risk ratios with 95% CIs were calculated. Compared with adults who were kept…

OBJECTIVES: Stress ulcer prophylaxis is commonly administered to critically ill patients for the prevention of clinically important stress-related mucosal bleeding from the upper gastrointestinal tract. Despite widespread incorporation of stress ulcer prophylaxis into practice around the world, questions are emerging about its indications and impact. This clinically focused article will review current controversies related to stress ulcer prophylaxis for critically ill adult patients, including bleeding frequency, risk factors, comparative efficacy, adverse effect profile, and overall cost-effectiveness of the available stress ulcer prophylaxis regimens. DATA SOURCES: A MEDLINE search was conducted from inception through August 2015. STUDY SELECTION: Selected publications describing stress ulcer prophylaxis in adult patients were retrieved (original research, systematic reviews, and practice guidelines); their bibliographies were also reviewed to identify additional pertinent publications. DATA EXTRACTION: Data from relevant publications were abstracted and summarized. DATA…

OBJECTIVE: In immunocompromised patients with acute respiratory failure, invasive mechanical ventilation remains associated with high mortality. Choosing the adequate oxygenation strategy is of the utmost importance in that setting. High-flow nasal oxygen has recently shown survival benefits in unselected patients with acute respiratory failure. The objective was to assess outcomes of immunocompromised patients with hypoxemic acute respiratory failure treated with high-flow nasal oxygen. DESIGN: We performed a post hoc analysis of a randomized controlled trial of noninvasive ventilation in critically ill immunocompromised patients with hypoxemic acute respiratory failure. SETTING: Twenty-nine ICUs in France and Belgium. PATIENTS: Critically ill immunocompromised patients with hypoxemic acute respiratory failure. INTERVENTION: A propensity score-based approach was used to assess the impact of high-flow nasal oxygen compared with standard oxygen on day 28 mortality. MEASUREMENTS AND MAIN RESULTS: Among 374 patients included in the study, 353 met inclusion criteria. Underlying disease…

OBJECTIVES: Autonomic impairment after acute traumatic brain injury has been associated independently with both increased morbidity and mortality. Links between autonomic impairment and increased intracranial pressure or impaired cerebral autoregulation have been described as well. However, relationships between autonomic impairment, intracranial pressure, impaired cerebral autoregulation, and outcome remain poorly explored. Using continuous measurements of heart rate variability and baroreflex sensitivity we aimed to test whether autonomic markers are associated with functional outcome and mortality independently of intracranial variables. Further, we aimed to evaluate the relationships between autonomic functions, intracranial pressure, and cerebral autoregulation. DESIGN: Retrospective analysis of a prospective database. SETTING: Neurocritical care unit in a university hospital. SUBJECTS: Sedated patients with severe traumatic brain injury. MEASUREMENTS AND MAIN RESULTS: Waveforms of intracranial pressure and arterial blood pressure, baseline Glasgow Coma Scale and 6 months…

OBJECTIVE: This study aimed to assess whether interventions targeted at improving sleep in the ICU were associated with reductions in ICU delirium. Secondary outcomes include duration of delirium and ICU length of stay. DATA SOURCES: MEDLINE, CINAHL, Web of Science, Scopus, WorldCat, and International Pharmaceutical Abstracts were searched from inception to January 2016. STUDY SELECTION: Studies investigating any type of sleep intervention (nonpharmacologic or pharmacologic) and assessing the impact on ICU delirium were included. Any type of study design was permitted so long as the delirium assessment was made at least daily with a validated delirium assessment tool. DATA EXTRACTION: The following data were extracted: first author, year of publication, study design, ICU type, components of sleep intervention, use of sleep assessment tool, patient age, sex, severity of illness, sleep measures, delirium assessment tool, incidence of delirium, duration of delirium, and ICU length of stay. The incidence of delirium was used to compare rates of ICU delirium across studies. Methodologic…

OBJECTIVE: While type 1 programmed cell death (apoptosis) of T cells leads to immunosuppression in sepsis, a crosstalk between apoptosis and autophagy (type 2 programmed cell death) has not been shown. The aim of this study is to elucidate the details of the interaction between autophagy and immunosuppression. DESIGN: Laboratory investigation in the murine sepsis model. SETTING: University laboratory. SUBJECTS: Six- to 8-week-old male mice. INTERVENTIONS: We investigated the kinetics of autophagy in T cells from spleen in a cecal ligation and puncture model with green fluorescent protein-microtubule-associated protein light chain 3 transgenic mice. We analyzed apoptosis, mitochondrial homeostasis and cytokine production in T cells, and survival rate after cecal ligation and puncture using T cell-specific autophagy-deficient mice. MEASUREMENTS AND MAIN RESULTS: We observed an increase of autophagosomes, which was assessed by flow cytometry. However, an autophagy process in CD4 T cells during sepsis was insufficient including the accumulation of p62. On the other hand, a blockade of…

OBJECTIVES: Moral distress is a common experience among critical care professionals, leading to frustration, withdrawal from patient care, and job abandonment. Most of the studies on moral distress have used the Moral Distress Scale or its revised version (Moral Distress Scale-Revised). However, these scales have never been validated through factor analysis. This article aims to explore the factorial structure of the Moral Distress Scale-Revised and develop a valid and reliable scale through factor analysis. DESIGN: Validation study using a survey design. SETTING: Eight medical-surgical ICUs in the north of Italy. SUBJECTS: A total of 184 clinicians (64 physicians, 94 nurses, and 14 residents). INTERVENTIONS: The Moral Distress Scale-Revised was translated into Italian and administered along with a measure of depression (Beck Depression Inventory-Second Edition) to establish convergent validity. Exploratory factor analysis was conducted to explore the Moral Distress Scale-Revised factorial structure. Items with low (less than or equal to 0.350) or multiple saturations were removed.…

OBJECTIVE: In response to a need for better sepsis diagnostics, several new gene expression classifiers have been recently published, including the 11-gene "Sepsis MetaScore," the "FAIM3-to-PLAC8" ratio, and the Septicyte Lab. We performed a systematic search for publicly available gene expression data in sepsis and tested each gene expression classifier in all included datasets. We also created a public repository of sepsis gene expression data to encourage their future reuse. DATA SOURCES: We searched National Institutes of Health Gene Expression Omnibus and EBI ArrayExpress for human gene expression microarray datasets. We also included the Glue Grant trauma gene expression cohorts. STUDY SELECTION: We selected clinical, time-matched, whole blood studies of sepsis and acute infections as compared to healthy and/or noninfectious inflammation patients. We identified 39 datasets composed of 3,241 samples from 2,604 patients. DATA EXTRACTION: All data were renormalized from raw data, when available, using consistent methods. DATA SYNTHESIS: Mean validation areas under the receiver…

OBJECTIVE: The histopathologic changes associated with septic acute kidney injury are poorly understood, in part, because of the lack of biopsy data in humans. Animal models of septic acute kidney injury may help define such changes. Therefore, we performed a systematic review of the histopathologic changes found in modern experimental septic acute kidney injury models. DATA SOURCES: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, and PubMed (from January 2007 to February 2015). STUDY SELECTION: We reviewed experimental studies reporting findings on the histopathology of contemporary experimental septic acute kidney injury. DATA EXTRACTION: We focused on the presence or the absence of acute tubular necrosis, tubular cell apoptosis, and other nonspecific findings. DATA SYNTHESIS: We identified 102 studies in 1,059 animals. Among the 1,059 animals, 53 (5.0%) did not have any renal histopathologic changes, but acute tubular necrosis was found in 184 (17.4%). The prevalence of acute tubular necrosis was not related to animal size or model of sepsis and was…

OBJECTIVE: Although mesenchymal stem/stromal cells represent a promising therapeutic strategy for acute respiratory distress syndrome, clinical translation faces challenges, including scarcity of bone marrow donors, and reliance on bovine serum during mesenchymal stem/stromal cell proliferation. We wished to compare mesenchymal stem/stromal cells from human umbilical cord, grown in xeno-free conditions, with mesenchymal stem/stromal cells from human bone marrow, in a rat model of Escherichia coli pneumonia. In addition, we wished to determine the potential for umbilical cord-mesenchymal stem/stromal cells to reduce E. coli-induced oxidant injury. DESIGN: Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Acute respiratory distress syndrome was induced in rats by intratracheal instillation of E. coli (1.5-2 × 10 CFU/kg). "Series 1" compared the effects of freshly thawed cryopreserved umbilical cord-mesenchymal stem/stromal cells with bone marrow-mesenchymal stem/stromal cells on physiologic indices of lung injury,…

OBJECTIVES: Treatment algorithms for cardiac arrest are rescuer centric and vary little from patient to patient. The objective of this study was to determine if cardiopulmonary resuscitation-targeted to arterial blood pressure and coronary perfusion pressure rather than optimal guideline care would improve 24-hour survival in a porcine model of ventricular fibrillation cardiac arrest. DATA SOURCES: Preclinical animal laboratory using female 3-month-old swine. STUDY SELECTION: A randomized interventional study. DATA EXTRACTION: After induction of anesthesia and 7 minutes of untreated ventricular fibrillation, 16 female 3-month-old swine were randomized to 1) blood pressure care: titration of chest compression depth to a systolic blood pressure of 100 mm Hg and vasopressor dosing to maintain coronary perfusion pressure of greater than 20 mm Hg or 2) guideline care: chest compression depth targeted to 51 mm and standard guideline vasopressor dosing. Animals received manual cardiopulmonary resuscitation for 10 minutes before the first defibrillation attempt and standardized…

OBJECTIVES: Pulmonary complications are common following hematopoietic stem cell transplantation. Numerous idiopathic post-transplantation pulmonary syndromes have been described. Patients at the severe end of this spectrum may present with hypoxemic respiratory failure and pulmonary infiltrates, meeting criteria for acute respiratory distress syndrome. The incidence and outcomes of acute respiratory distress syndrome in this setting are poorly characterized. DESIGN: Retrospective cohort study. SETTING: Mayo Clinic, Rochester, MN. PATIENTS: Patients undergoing autologous and allogeneic hematopoietic stem cell transplantation between January 1, 2005, and December 31, 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were screened for acute respiratory distress syndrome development within 1 year of hematopoietic stem cell transplantation. Acute respiratory distress syndrome adjudication was performed in accordance with the 2012 Berlin criteria. In total, 133 cases of acute respiratory distress syndrome developed in 2,635 patients undergoing hematopoietic stem cell…

OBJECTIVES: Sepsis generates significant global acute illness burden. The international variations in sepsis epidemiology (illness burden) have implications for region specific health policy. We hypothesised that there have been changes over time in the sepsis definitional elements (infection and organ dysfunction), and these may have impacted on hospital mortality. DESIGN: Cohort study. SETTING: We evaluated a high quality, nationally representative, clinical ICU database including data from 181 adult ICUs in England. PATIENTS: Nine hundred sixty-seven thousand five hundred thirty-two consecutive adult ICU admissions from January 2000 to December 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: To address the proposed hypothesis, we evaluated a high quality, nationally representative, clinical, ICU database of 967,532 consecutive admissions to 181 adult ICUs in England, from January 2000 to December 2012, to identify sepsis cases in a robust and reproducible way. Multinomial logistic regression was used to report unadjusted trends in sepsis definitional elements and in…

OBJECTIVES: Functional status at hospital discharge may be a risk factor for adverse events among survivors of critical illness. We sought to examine the association between functional status at hospital discharge in survivors of critical care and risk of 90-day all-cause mortality after hospital discharge. DESIGN: Single-center retrospective cohort study. SETTING: Academic Medical Center. PATIENTS: Ten thousand three hundred forty-three adults who received critical care from 1997 to 2011 and survived hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure of interest was functional status determined at hospital discharge by a licensed physical therapist and rated based on qualitative categories adapted from the Functional Independence Measure. The main outcome was 90-day post hospital discharge all-cause mortality. A categorical risk-prediction score was derived and validated based on a logistic regression model of the function grades for each assessment. In an adjusted logistic regression model, the lowest quartile of functional status at hospital…

OBJECTIVE: To compare the ability of medical emergency team criteria and the National Early Warning Score to discriminate cardiac arrest, unanticipated ICU admission and death within 24 hours of a vital signs measurement, and to quantify the associated workload. DESIGN: Retrospective cohort study. SETTING: A large U.K. National Health Service District General Hospital. PATIENTS: Adults hospitalized from May 25, 2011, to December 31, 2013. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We applied the National Early Warning Score and 44 sets of medical emergency team criteria to a database of 2,245,778 vital signs sets (103,998 admissions). The National Early Warning Score's performance was assessed using the area under the receiver-operating characteristic curve and compared with sensitivity/specificity for different medical emergency team criteria. Area under the receiver-operating characteristic curve (95% CI) for the National Early Warning Score for the combined outcome (i.e., death, cardiac arrest, or unanticipated ICU admission) was 0.88 (0.88-0.88). A National Early…

OBJECTIVES: Despite being the epicenter of recent pandemics, little is known about critical care in Asia. Our objective was to describe the structure, organization, and delivery in Asian ICUs. DESIGN: A web-based survey with the following domains: hospital organizational characteristics, ICU organizational characteristics, staffing, procedures and therapies available in the ICU and written protocols and policies. SETTING: ICUs from 20 Asian countries from April 2013 to January 2014. Countries were divided into low-, middle-, and high-income based on the 2011 World Bank Classification. SUBJECTS: ICU directors or representatives. MEASUREMENTS AND MAIN RESULTS: Of 672 representatives, 335 (50%) responded. The average number of hospital beds was 973 (SE of the mean [SEM], 271) with 9% (SEM, 3%) being ICU beds. In the index ICUs, the average number of beds was 21 (SEM, 3), of single rooms 8 (SEM, 2), of negative-pressure rooms 3 (SEM, 1), and of board-certified intensivists 7 (SEM, 3). Most ICUs (65%) functioned as closed units. The nurse-to-patient ratio was 1:1 or 1:2 in most ICUs…

OBJECTIVE: There is only limited knowledge about chronic pain conditions resulting from critical care. Experimental and clinical data suggest a close relationship between inflammation and pain perception. Since sepsis is the most severe form of systemic inflammation, the primary objective was to evaluate chronic pain states and functional impairment of septic and nonseptic patients 6 months after discharge from ICU. Second, we aimed to obtain the total prevalence and characteristics of chronic ICU-related pain. DESIGN: Case-control study. SETTING: Observational study in long-term survivors of mixed surgical and medical ICUs. PATIENTS: Septic and nonseptic survivors of critical care (n = 207) and healthy controls (n = 46). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We collected comprehensive information on patients' past and present pain 6 months after ICU discharge by means of the German pain questionnaire. Pain intensity levels and pain interference ratings were compared between septic and nonseptic patients and healthy controls. We found no differences in prevalence,…

OBJECTIVES: To determine whether delirium during ICU stay is associated with long-term mental health problems defined as symptoms of anxiety, depression, and posttraumatic stress disorder. DESIGN: Prospective cohort study. SETTING: Survey study, 1 year after discharge from a medical-surgical ICU in the Netherlands. PATIENTS: One-year ICU survivors of an ICU admission lasting more than 48 hours, without a neurologic disorder or other condition that would impede delirium assessment during ICU stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One year after discharge, ICU survivors received a survey containing the Hospital Anxiety and Depression Scale with a subscale for symptoms of depression and a subscale for symptoms of anxiety, and the Impact of Event Scale 15 item measuring symptoms of posttraumatic stress disorder. Participants were classified as having experienced no delirium (n = 270; 48%), a single day of delirium (n = 86; 15%), or multiple days of delirium (n = 211; 37%) during ICU stay. Log-binomial regression was used to assess the association between delirium and…

OBJECTIVES: Inadequate stratification of septic shock patients may result in inappropriate treatment allocation in randomized clinical trials, especially regarding anticoagulant. We previously reported that endothelial-derived microparticles are relevant biomarkers of sepsis-induced disseminated intravascular coagulation. In this validation cohort, we assess microparticles as surrogates of cell activation to improve early disseminated intravascular coagulation diagnosis and patient stratification. DESIGN: Prospective observational study in septic shock patients. SETTINGS: Four medical ICUs in university hospitals. PATIENTS AND METHODS: Two hundred sixty-five patients with septic shock from four ICUs were consecutively enrolled. Disseminated intravascular coagulation was diagnosed according to Japanese Association for Acute Medicine 2006 score. Endothelial- and leukocyte-derived circulating procoagulant microparticles were isolated and quantified by prothrombinase assay at admission, day 3, and day 7. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Two hundred fifty-nine patients…

OBJECTIVE: Blunt trauma patients may present with similar demographics and injury severity yet differ with regard to survival. We hypothesized that this divergence was due to different trajectories of systemic inflammation and utilized computational analyses to define these differences. DESIGN: Retrospective clinical study and experimental study in mice. SETTING: Level 1 trauma center and experimental laboratory. PATIENTS: From a cohort of 493 victims of blunt trauma, we conducted a pairwise, retrospective, case-control study of patients who survived over 24 hours but ultimately died (nonsurvivors; n = 19) and patients who, after ICU admission, went on to be discharged(survivors; n = 19). INTERVENTIONS: None in patients. Neutralizing anti-interleukin-17A antibody in mice. MEASUREMENTS AND MAIN RESULTS: Data on systemic inflammatory mediators assessed within the first 24 hours and over 7 days were analyzed with computational modeling to infer dynamic networks of inflammation. Network density among inflammatory mediators in nonsurvivors increased in parallel with organ dysfunction…

OBJECTIVES: To define the features of human amniotic mesenchymal stromal cell secretome and its protective properties in experimental models of acute brain injury. DESIGN: Prospective experimental study. SETTING: Laboratory research. SUBJECTS: C57Bl/6 mice. INTERVENTIONS: Mice subjected to sham or traumatic brain injury by controlled cortical impact received human amniotic mesenchymal stromal cells or phosphate-buffered saline infused intracerebroventricularly or intravenously 24 hours after injury. Organotypic cortical brain slices exposed to ischemic injury by oxygen-glucose deprivation were treated with human amniotic mesenchymal stromal cells or with their secretome (conditioned medium) in a transwell system. MEASUREMENTS AND MAIN RESULTS: Traumatic brain injured mice receiving human amniotic mesenchymal stromal cells intravenously or intracerebroventricularly showed early and lasting functional and anatomical brain protection. cortical slices injured by oxigen-glucose deprivation and treated with human amniotic mesenchymal stromal cells or conditioned medium showed comparable…

OBJECTIVES: Angiopoietins modulate endothelial permeability via endothelial cell junctions. Angiopoietin-2 blocks the angiopoietin-1/Tie-2 interaction that stabilizes these junctions, and elevated plasma angiopoietin-2 levels are associated with vascular leakage. We hypothesized that plasma angiopoietin-1 and angiopoietin-2 levels are associated with indirect markers of increased vascular permeability, organ dysfunction, mortality, and plasma proinflammatory cytokine levels in human septic shock. DESIGN: Multicenter observational cohort study derived from a randomized controlled trial (Vasopressin and Septic Shock Trial of vasopressin versus norepinephrine in septic shock). SETTING: ICUs of hospitals in Canada, Australia, and the United States. PATIENTS: Three hundred forty-one patients in the randomized, controlled Vasopressin and Septic Shock Trial trial of vasopressin versus norepinephrine in septic shock. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We measured plasma levels of angiopoietin-1 and angiopoietin-2 at study baseline and determined their association with…